Gaucher Disease: A Boy With Abdominal Enlargement and Pain

Samantha Schrier Vergano, MD, and Jennifer Ibrahim, MD

Samantha Vergano, MD, and Jennifer Ibrahim, MD

Vergano S, Ibrahim J. Gaucher disease: a boy with abdominal enlargement and pain. Consultant for Pediatricians. 2016;15(3):130-132.


An 8-year-old boy presented to his pediatrician with a grossly enlarged abdomen (Figure 1) and a several-month history of worsening abdominal pain, tightness, and discomfort, but with no nausea or vomiting. He also had been experiencing decreased appetite, fatigue, and easy bruising.

His gestation and birth had been uncomplicated, and his overall childhood health was good except for the increasingly large abdomen and a recent decrease in energy. His mother noted that the boy’s abdomen had always been big, but only recently did he complain of pain. Family history was not significant for any childhood illnesses or chronic conditions beginning in childhood. He has an older brother with autism and a younger sister with a repaired cleft palate.

Physical examination revealed gross abdominal distention with the spleen tip palpable in the groin, hepatomegaly to approximately 7 cm below the costal margin, mild muscle wasting in the extremities, and marked pallor. No neurologic symptoms were observed.

Results of a complete blood count were abnormal, with a hemoglobin concentration of 10.2 g/dL (reference range, 11.5-15.5 g/dL), a hematocrit of 30.3% (reference range, 34.5%-46.5%), a mean corpuscle volume of 72.8 µm3 (reference range, 78-100 µm3), and a platelet count of 165 × 103/µL (reference range, 150-450 × 103/µL). His ferritin level was elevated at 423 ng/mL (reference range, 10-60 ng/mL).

The patient was referred to a hematologist/oncologist for investigation of suspected malignancy. No malignant cells were identified on bone marrow biopsy, but macrophages were described as having the appearance of “crumpled tissue paper,” and irregular lysosomal structures were seen.

Given the bone marrow biopsy findings and the patient’s physical examination findings, the genetic disorder Gaucher disease (GD, also called acid β-glucosidase deficiency) was suspected. The patient was referred for genetic analysis.

Genetic Analysis Results

Genotype analysis, lysosomal enzyme analysis, laboratory analysis of common biomarkers of GD progression, computed tomography (CT) of the abdomen for organomegaly, magnetic resonance imaging (MRI) of the bilateral hips, and a dual-energy X-ray absorptiometry (DXA) to assess bone manifestations of GD were ordered according to recommended guidelines.1,2

Mutation analysis of the acid β-glucocerebrosidase gene (GBA) showed one L444P mutation, associated with GD type 3 (neuronopathic), and a variant of unknown significance (p.Ile93Leu). Analysis of lysosomal enzymes demonstrated low acid β-glucosidase activity. Laboratory analysis showed elevated levels of the following common biomarkers of GD progression: tartrate-resistant acid phosphatase, 85.1 U/L (reference range, < 10 U/L); chitotriosidase, 18,969 µmol/L/h (reference range, 120 µmol/L/h); and angiotensin, 425 U/L (reference range 25-106 U/L).

Abdominal CT revealed a moderately enlarged liver volume of 1652 mL and a markedly enlarged spleen volume of 1884 mL. MRI showed the gross enlargement of the liver and spleen (Figure 2). MRI of the bilateral hips showed diffuse increased T1 signal throughout the visualized metaphysis and diaphysis of the femurs bilaterally, with greatest involvement in the femoral necks. No evidence of avascular necrosis was observed. The lumbar spine showed diffuse lumbosacral spinal bone marrow involvement.

DXA revealed a Z score of 1.0 in the anteroposterior spine, which is at the lower limit of normal (reference range, –1 to +1), and a Z score of 1.0 for total bone mineral density.

The primary treatment for GD, enzyme replacement therapy, corrects the enzymatic deficiency in order to meet defined therapeutic goals.2,3 The patient received imiglucerase every 2 weeks, which he tolerated well. A daily multivitamin and iron supplementation for anemia also were recommended.

At follow-up at 9 years 1 month of age, the boy showed normal abdominal girth (Figure 3), decreased spleen and liver size, normal hematocrit and hemoglobin levels, and increased energy and stamina.


GD is a rare, autosomal recessive, heterogeneous, inborn error of metabolism caused by a deficiency of the lysosomal enzyme acid β-glucosidase. It leads to the accumulation of glucosylceramide within lysosomes of tissue macrophages in multiple organs. GD is categorized into 3 types: nonneuronopathic (GD1), acute neuronopathic (GD2), and chronic neuronopathic (GD3).4 GD1 accounts for more than 90% of known cases.5

Common disease manifestations in children with GD1 include splenomegaly (95%), hepatomegaly (87%), anemia (40%), thrombocytopenia (50%), and significant growth retardation (52% at or below the 25th percentile); 81% have at least 1 radiologic skeletal abnormality at the time of diagnosis.6

Persons with GD3 can present with or without neurologic symptoms; the majority present with moderate to severe hematologic and visceral manifestations.7 The similarity in the presentations of GD1 and GD3 can make it difficult to determine the type early in the disease course. GD2 is the most severe form of GD with early, devastating neurologic symptoms, and it typically is lethal within the first few years of life. Early neurologic signs of GD2 and GD3 can include eye movement abnormalities (eg, horizontal supranuclear gaze palsy) and developmental delays.7

When symptoms of GD appear in childhood, the course of the disease is typically more severe.4 Treatment with enzyme replacement therapy reduces or resolves manifestations of the disease, including splenomegaly, hepatomegaly, anemia, thrombocytopenia, growth retardation, bone pain, and loss of bone density.1,2,8,9 Progressive bone disease is the greatest source of morbidity and disability in persons with GD.10 The availability of therapies that may prevent or reverse early signs of GD-related bone disease increases the need for awareness among pediatric clinicians to aid in the expeditious diagnosis and treatment of children with symptoms of GD.

Our patient’s GD was diagnosed after a relatively short period of abdominal pain but an extended period of abdominal distention. Any child with a grossly enlarged abdomen should raise concern for organomegaly. The age of onset in GD has wide variability, but more than half of patients present before age 10.11 GD may be mistaken for other disease processes or even overlooked, with delays in diagnosis averaging 4 years.12 Symptoms can mimic more common pediatric concerns such as gastrointestinal tract problems, but the persistence of these symptoms is a significant sign requiring investigation for malignancy and genetic disease. Malignancy is one of the primary considerations, and its exclusion is imperative.13

Pediatricians also should recognize hepatosplenomegaly, anemia, and a low platelet count as presenting signs of GD, although the clinical presentation of GD has wide variability.5 While GD often is associated with Ashkenazi Jewish ancestry,14 the absence of this ethnic background should never exclude consideration of GD in the differential diagnosis.

Our patient’s bone marrow biopsy results were suggestive of GD, and the child was referred for genetic analysis. GD was confirmed through acid β-glucosidase enzyme analysis and GBA genotyping. At present, genotype/phenotype correlation in GD is limited, and the type cannot be predicted solely by residual enzyme level or mutation; therefore, designation of type is based on clinical assessment.15 Our patient had 1 mutation that is associated with GD3, but no neurologic involvement was evident, complicating his GD type designation.

This case illustrates the need to consider GD in the differential diagnosis of children with persistent hepatosplenomegaly, anemia, and thrombocytopenia. GD is rare and may present similarly to other more common conditions; as such, it is easily misdiagnosed or overlooked. This can delay the diagnosis of this rare but treatable disorder, potentially into adulthood, which can lead to irreversible consequences.12

Samantha Schrier Vergano, MD, is an attending physician in the Division of Medical Genetics and Metabolism at Children’s Hospital of The King’s Daughters in Norfolk, Virginia.

Jennifer Ibrahim, MD, is the US Medical Director at Genzyme, a Sanofi Company, in Cambridge, Massachusetts.


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2. Kaplan P, Baris H, De Meirleir L, et al. Revised recommendations for the management of Gaucher disease in children. Eur J Pediatr. 2013;172(4): 447-458.

3. Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41(4 suppl 5):4-14.

4. Grabowski GA, Petsko GA, Kolodny EH. Gaucher disease. In: Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill:chap 146.
http://ommbid.mhmedical.com/content.aspx?sectionid=62643884&bookid=971&Resultclick=2&q=gaucher. Accessed February 16, 2016.

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6. Kaplan P, Andersson HC, Kacena KA, Yee JD. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med. 2006;160(6):603-608.

7. Tylki-Szymańska A, Vellodi A, El-Beshlawy A, Cole JA, Kolodny E. Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry. J Inherit Metab Dis. 2010;33(4):339-346.

8. Anderson LJ, Henley W, Wyatt KM, et al. Long-term effectiveness of enzyme replacement therapy in children with Gaucher disease: results from the NCS-LSD cohort study. J Inherit Metab Dis. 2014;37(6):961-968.

9. Weinreb NJ, Goldblatt J, Villalobos J, et al. Long-term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment. J Inherit Metab Dis. 2013;36(3):543-553.

10. Maas M, Hangartner T, Mariani G, et al. Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease. Skeletal Radiol. 2008;37(3):185-188.

11. Charrow J, Andersson HC, Kaplan P, et al. The Gaucher Registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000;160(18):2835-2843.

12. Mistry PK, Sadan S, Yang R, Yee J, Yang M. Consequences of diagnostic delays in type 1 Gaucher disease: the need for greater awareness among hematologists-oncologists and an opportunity for early diagnosis and intervention. Am J Hematol. 2007;82(8):697-701.

13. Mistry PK, Cappellini MD, Lukina E, et al. A reappraisal of Gaucher disease—diagnosis and disease management algorithms. Am J Hematol. 2011;86(1):110-115.

14. Grabowski GA. Phenotype, diagnosis, and treatment of Gaucher’s disease. Lancet. 2008;372(9645):1263-1271.

15. Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008;29(5):567-583.

Disclosures and Acknowledgement

Samantha Schrier Vergano, MD, has received no compensation, honoraria, or other financial incentive from Genzyme, a Sanofi Company, and has no financial interest in the company. She is on the advisory board of Ambry Genetics, a company unrelated to Genzyme or this case report and that provides no compensation.

Jennifer Ibrahim, MD, is an employee of Genzyme, a Sanofi Company, and receives a salary from Genzyme.

Genzyme, a Sanofi Company, provided financial assistance for the writing and submission of the manuscript.

The authors acknowledge the assistance of Laura Croal, Medical Communication and Education Manager—Rare Diseases, at Genzyme, a Sanofi Company, who assisted with conceptualization, reviewing, and editing the manuscript; Shelton Panak, a medical writer contracted through Strategic Research and Scientific Communications, LLC, who assisted with writing, editing, preparation, and submission of the manuscript; and Cheryl Lathrop, a medical writer at Genzyme, a Sanofi Company, who assisted with conceptualization and outline preparation of the manuscript.